Pharmaceutical product from the suprarenal glands and process of obtaining the same.



UITED STATES.- PATEET Enron.

WTLLAED-oEL-TG E, or DETROIT, MICHIGAN, .assrenon To FREDERICK s EAENs a COMiEANY, or DETROIT, MICHIGAN, A ooEroEATIoN OF MICHIGAN.

PHARMACEUTICAL PRODUCT FROM THE SUPRARENAL GLANDS AND PROCESS OF OBTAINING THE SAME.

ED035646. No Drawing,

Specification of Iietters Patent. 7 Patented Sept, 19-, 1911,, Application filed January 1o, 1905. Serial No. 240,502.-

To'dll it may concern:

jBe it known that I, WILLARD OHLIGER, residing at Detroit, in the county of Wayne and State of Michigan, a citizen of the United States, have invented certain, new and useful Improvements in Pharmaceutical'Products from the Suprarenal Glands and-Processes of Obtaining the Same, of which the following is a specificationl It is the object of the invent-ion .to .obtain a product in the form of'a sol ution containing the blood-pressure-rai'sing constituents of the suprarenal glands, comparatively fi tefrom impurities and possessing greater sit-ability than productsheretofore obtained. ;It ,is" a,'.further objectftoobtain from the glands an'increased yield 'of the desired product.

With these objects in view, the invention consists, first, in the process of extracting and purifying the product, the latter being at'no time precipitated, but remaining in solution "from start to finish; second', in the means employed .for protecting the product froin decoinposition during the process of purification; third, in the association With the product, in its purifiedcondition, of a substance imparting stability, without modifying its physiological characteristics. In the preparation of blood-pressureraising products from the suprarenal gl'ands,'itjis usual to precipitate the prodnot in a crude'fo'rm from the fluid extract of the glands, and to then purify this product by re-dissolving andprecipitating it a number of times. Each time the product is thus precipitated, there is a loss, 11. e. a certain percentage cannot be thrownout of the solution'. I its .a consequence, the more frequent the "precipitation, the smaller will be the yield. A further source of loss is due to oxidation of decomposition of a portion 'of the product during treatment. This loss is diminishedby protecting the-fluid extract from the air, as by a'filni of fat" on the top offthe liquid, but nevertheless a certain portion of the product is destroyed.-

VVit-h my ijrnproved process,-loss of;the product is pjievanti d first, by maintaining it in solu gradually deteriorating,.this action being hastened by exposure vto'light. My improvedproduet is practically stable in solution. As first obtained, it is colorless, and after weeks standing and exposure to sunlight, it remains unchanged.

In carrying out my process, the first. step is to. obtain'a fiuid' extract of'the glands. This is preferably accomplished by the'use of an acidified alcohol, the acid rendering the desired product more readily soluble than in pure alcohol... In detail, the glands are first freed from adherent fat and tissue .and are then finely minced by -suitable means. They are then placed in acidified alcohol, methyl alcohol and tri-chlor-acetic acid being preferred, and in a proportion of about five or six per cent. of the acid. The quantity of alcohol used for agiven weight of glands is preferably about'l' to 2.. To prevent oxidation of the active principle during the maceration and digestion of the glands, a small quantity of a suitable reducing agent is added to the solution, as for instance 0.25% of sodium sinfite; In place of this, other reducing agents, asfor example hydrogen sulfite, sulfur dioxid and zinc may be used. The presence of this active reducing agent effectually prevents oxidation of the active principle during this first step of the process. In adding the acidulated alcohol to the glands, great care is taken that the acid alcohol well penetrates the tissues instead of merely coagulating the individual particles. The mixture is then digested. at a temperature of about de greesG; for twelve hours, after Whichthe;

. metal is then filtered out.

uid obtained, a further addition of the retract and thus, the liquid when pressed out, is almost colorless The liquid is next heated to the boiling point in an open vessel to coagulate a part of the proteids. It is then filtered and the colorless filtrate condensed preferably underdiminished pres- Sure to about one-sixth of its volume. In case of further precipitation of inert substances during concentration, the liquid is again filtered. The liquid thus obtained still contains proteids. nated' by the addition of soluble metallic salts, such as neutral lead-acetate or zinc chlorid, which throw down the proteids as a precipitate. The mixture is allowed to stand'for several hours after the precipitate has settled and the clear liquid is decanted or filtered off. To eliminate any excess of the metallic salts still remaining in the solution, hydrogen sulfid gas is added, the liquid being, constantly stirred. The precipitated To the clear liqducing agent is made, preferably 0.5% of sodium sulfite and in case the solution is rendered alkaline by this addition, hydrochloric acid is also added. The quantity addedis such as to render the solution slightly acid. For commercial use, the solution thus obtained is diluted with well boiled distilled water, so that 1 cc. of the solution will represent 1 gm. of the gland. The finished solution is neutralized by the addition of N/ solution of potassium hydrate, in the proportion of about 12 cc. of the potassium hydrate to 10 cc. of the solution. If still too acid, sufiicient sodium hydrate is added to bring the solution to proper acidity.

The final solution has the form of a clear practically colorless liquid. Itreduces ammoniacal solution of silver and assumes temporarily an intensely green color on addiof the blood-pressure-raising substance of the suprarenal glands and an associated reduclng agent.

2. The process of obtaining a purified fluid extract of the blood pressure raising substance from the suprarenal glands which consists in forming a fluid extract of the glands bythe use of alcohol and tri-chloracetic acid, in boiling'said extract to precipitate out nonactive bodies, in concentrating the extract, in' preclpitating out the remainingnonactive bodies by the addition of soluble metallic salts, in eliminatin the excess of said soluble salts by precipitation,

with a volatile precipitant and in performing all of the steps of the process inthe These are next elimistituents therefrom while under the action of said reducing agent.

5. In the herein-described process of obtaining the blood-pressure-raising substance from the suprarenal glands, the steps which consist in extracting the glands with acidified alcohol, in then concentrating and eliminating further impurities by r'e-agents other than acidified alcohol.

6. In the herein-described process of obtaining the blood-pressure-raising substance frpm the suprarenal glands, the steps which consist in first extracting the glands with' acidified methyl alcohol and then concentrating the extract and eliminating impurities by re-agents other than acidified methyl alcohol.

7. In the herein-described process of obtaining the blood-pressure-raising substance from the suprarenal glands, the' steps which consist in extracting the glands with alcohol and tri-chlor-acetic acid, in then concentrating the extract and further eliminating the impurities by re-agents other than tri-chloracetic acid. 1

8. In the process of obtaining a purified fluid extract of the blood-pressure-raising substance from the suprarenal glands, the

steps which consist in forming a fluid extract of the glands, and in precipitating nonactive constituents therefrom by the addition of metallic salts, and in removing the precipitate and the excess of said metallic salts, while maintaining the active substance in solution.

9. In the process of obtaining the bloodpressure-raislng substance from the suprarenal glands, the steps which consist in forming an alcoholic extract of the glands, in concentrating the extract and in precipitating remaining non-active bodies from the solution by metallic salts.

10. In the herein-described process of obtaining the blood-pressure-raising substance from the suprarenal glands, the steps which consist in forming an alcoholic extract of the glands, in boiling said extract to precipitate out non-active bodies, in then concentrating the extract and precipitating out. re- '7 of soluble metallic salts and in eliminating 10 'maining non-active bodies, by addition of the excess of said soluble salts by avolatile metallic salts. precipitant.

11. In the herein-described process of 0b- In testimony whereof I aflix my signatur taining the blood-pressu're-raising substance in presence of two Witnesses. from the suprarenal glands, the steps which WILLARD OHLIGER. consist in forming a fluid extract of the Witnesses: glands, concentrating said extract, precipi- H. C. SMITH, tating out non-active bodies by the addition En. d). AULT. 

